title: TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis.
abstract: Visceral leishmaniasis (VL) or Kala-azar is a serious protozoan infectious disease caused by an obligate intracellular parasite. Cytokines have a major role in determining progression and severity of clinical manifestations in VL. We investigated polymorphisms in the TGFB1and IL8 genes, which are cytokines known to have a role in onset and severity of the disease. Polymorphisms at TGFB1 -509 C/T and +869 T/C, and IL8 -251 A/T were analyzed by a PCR-RFLP technique, in 198 patients with VL, 98 individuals with asymptomatic infection positive for a delayed-type hypersensitivity test (DTH+) and in 101 individuals with no evidence of infection (DTH-). The presence of the T allele in position -509 of the TGFB1 gene conferred a two-fold risk to develop infection both when including those with clinical symptoms (DTH+ and VL, grouped) or when considering DTH+ only, respectively p = 0.007, OR = 1.9 [1.19-3.02] and p = 0.012, OR = 2.01 [1.17-3.79], when compared with DTH- individuals. In addition, occurrence of hemorrhage was associated with TGFB1 -509 T allele. We suggest that the -509 T allele of the TGFB1 gene, a cytokine with a biologically relevant role in the natural history of the disease, may contribute to overall susceptibility to infection by Leishmania and to severity of the clinical disease.
authors.affiliation: Laboratory of Immunology, Heart Institute, InCor, HC-FMUSP, SP, Brazil.
authors.forename: Amanda Farage
authors.initials: AF
authors.lastname: Frade
authors.forename: Lea Campos de
authors.initials: LC
authors.lastname: Oliveira
authors.forename: Dorcas Lamounier
authors.initials: DL
authors.lastname: Costa
authors.forename: Carlos Henrique Nery
authors.initials: CH
authors.lastname: Costa
authors.forename: Dorlene
authors.initials: D
authors.lastname: Aquino
authors.forename: Johan
authors.initials: J
authors.lastname: Van Weyenbergh
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Anna Carla
authors.initials: AC
authors.lastname: Goldberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000235:genetics*; D007898:Leishmaniasis, Visceral / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D016209:Interleukin-8; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1